Multi-system Connective Tissue Disease Flashcards
What is Systemic Lupus Erythematosus?
SLE
Multi system autoimmune inflammatory disease in which autoantibodies to a variety of autoantigens result in the formation and deposition of immune complexes.
Which are the systems which are affected in SLE and what are the constitutional symptoms?
Systems affected:
- CNS
- Heart
- Lung
- Renal
- MSK
- Skin
Constitutional symptoms:
- Fatigue
- Weight loss
- Fever
- Myalgia
Outline the specific systems based symptoms of SLE?
Skin:
- Malar photosensitive rash sparing the nasolabial folds
- Discoid erythematous rash (chest and face)
MSK:
- Arthritis usually involves peripheral joints
- Often migratory may affect joints for a short period of time before affecting another joint
- Deforming arthropathy (Jaccoud’s)
Renal:
- Proteinuria/ GN
- Increased BP
Cardiac:
- Pericarditis, valve disease, athersclerosis
Respiratory:
- Pneumonitis, pul fibrosis, pleural effusions
CNS:
- Seizures
- Psychosis
- depression
Haematological:
- Low WCC
- Low Platelets
- anaemia
- May have Autoimmune haemolytic anaemia
Which autoantibodies are associated with SLE and which is most associated?
ANA +ve in 95% of patients with SLE (sensitive)
dsDNA (very specific for SLE) but only present 60% of the time (associated with poor prognosis)
Anti ENA’s (extranuclear antibodies) 30% of patients
- Sm (only SLE)
- Ro*
- La*
- RNP*
*Often present in SLE but also in other connective tissue disorders such as Sjogren’s
Outline the investigations of a patient with suspected SLE?
Routine bloods and urinalysis.
- U+E, FBC, ESR (raised), CRP
Immunological bloods:
- ANA autoantibodies
- dsDNA antibodies
- Anti ENA (Ro, La, SM, RNP)
- Anticardiolipin antibodies (false +ve syphylis serology)
Imaging:
- CXR/CT if respiratory symptoms (may see fibrosis)
- MRI head if neuro symptoms
Invasive:
- Renal biopsy may be indicated in the presence of renal symptoms.
Outline a classical history of a patient presenting with SLE which would warrant further investigation?
Fever, joint pain and a rash in a women of child bearing age.
Using the mnemonic SOAPBRAIN describe the features of SLE?
- Serositis (inflammation of membranous linings)
- Oral ulcers
- Arthritis
- Photosensitivity
- Blood disorders
- Renal involvement
- Antinuclear antibodies (ANA)
- Immunologic phenomena (eg, dsDNA; anti-Smith [Sm] antibodies)
- Neurologic disorder
- Malar rash
- Discoid rash
Describe the management of SLE?
Simple disease:
- NSAIDs
- Lifestyle measures are used (avoid the sun use sun screen)
Disease modifying drugs in moderate disease:
- Hydroxychloroquine is often used.
- Corticosteroids can be used in short doses or severe disease.
- Azathioprine can be used as a steroid sparing agent
Severe disease:
- Cyclophosphamide (chemo agent can be used)
- Methotrexate
- Ciclosporin
What is antiphospholipid syndrome?
It is a condition in which the presence of antiphospholipids (anti-cardiolipin and lupus anticoagulant) cause a predispostion to clotting
Paradoxically this is due to a disruption in the clotting cascade so despite the predisposition to clotting patients have a prolonged APTT.
Describe the different aetiology of antiphospholipid syndrome?
It can either be a primary autoimmune disorder; 70% of cases.
Or can be secondary to SLE; 30% of cases
How do patients with anti-phospholipid syndrome present?
What other symptoms may a patient with APL have?
Most commonly presents in women who have had recurrent miscarriage.
May present with venous or arterial clots.
May also have livedo reticularis, thrombocytopenia, migraines, epilepsy, leg ulcers, haemolytic anaemia, heart valve disease, renal impairment
Describe the treatment of antiphospholipid syndrome?
It is managed with low dose aspirin, often prevents miscarriage.
Lifestyle advice e.g. avoid prolonged immobilisation
If recurrent clots venous anticoagulation is needed: warfarin target INR 3.5 or a DOAC (lifelong)
If pregnant given LMWH and aspirin, early delivery preferred.
Describe the clinical features of limited systemic sclerosis?
CREST Syndrome
- Calcinosis
- Raynauds
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
Skin involvement is limited to the elbow
Patients will not be able to open there mouth very wide (microstomia)
Describe the clinical features of diffuse systemic sclerosis?
Diffuse skin involvement and organ fibrosis
Cardiac: arrhythmias, myocardial fibrosis, pericarditis, myocarditis, valve problems
Lung: fibrosis and pulmonary hypertension
GI: GORD, aspiration, dysphagia, anal incontinence, dysmotility, constipation, malabsorbtion
Renal: acute hypertensive crisis (commonest cause of death)
- Which autoantibody is present in limited system sclerosis?
- Which are present in diffuse?
- Anti-centromere antibody (ACA)
2.
Anti-topoisomerase 1 (particularly in lung fibrosis)
Anti-RNA polymerase III (particularly in renal involvement)
Anti-sd-70
Describe the treatment of systemic sclerosis?
Conservative:
- Exercise and skin lubricants: reduce contractures
- Hand warmers
Medical:
- Immunosuppression in generalised
- Raynaud’s: Ca channel blockers, ACEi, sympathectomy
- Renal: intensive BP control: ACEi 1st line
- Oesophageal: PPIs, prokinetics (metoclopramide)
Surgical
- Remove calcinoses
What are the clincal features of Sjogren’s?
Also known as Keratoconjunctivitis Sicca
Specific features: (dry membranes)
- Xeropthalmia = Dry eyes (reduced tear production)
- Xerostomia (reduced salivation)
- Bilateral parotid swelling
- Vaginal dryness causing dyspareunia
Systemic symptoms:
- Polyarthritis
- Raynaud’s
- Bibasal pulmonary fibrosis
- Vasculitis
- Myositis
Describe the investigations you would do for Sjogren’s?
Schirmer tear test
Abs:
- ANA–Ro (70%+ve) and La (30%)
- Rheumatoid factor (nearly 100% are raised)
- ANA (+ve 70%)
If Parotid swelling (biopsy)
Describe the associated diseases to Sjogren’s?
Can be secondary to:
- Systemic sclerosis
- SLE
- RA
- Polymyositis
Also assocaited with autoimmune conditions and MALT lymphoma
Descirbe the management of Sjogren’s disease?
Artificial tears
Saliva replacement solutions
NSAIDs and hydroxychloroquine for arthralgia
Describe the clinical features of polymyositis and dermatomyositis?
Progressive symmetrical proximal muscle weakness.
Eventually may progress to dysphagia, dysphonia, respiratory weakness.
In dermatomyositis there are also skin changes:
- Heliotrope rash on eyelids ± oedema
- Macular rash (shawl sign +ve: over back and shoulders)
- Nailfold erythema
- Gottron’s papules: knuckles, elbows, knees (red eczematous rash)
Both are often paraneoplastic syndromes (paticularly in dermatomyositis)
Describe how you would investigate for Polymyositis or Dermatomyositis?
- Muscle enzymes (CK, LDH)
- ANA (+ve in 5-%)
- Anti Jo1 antibodies
- EMG (electromyography) or MRI to find location for biopsy. Then needle muscle biopsy (shows fibre necrosis)
- CT or endoscopy to screen for Malignancy
Describe how you would manage polymyositis/deramtomyositis?
Screen for Malignancy
Immunsupression:
- Corticosteroids
- Azathioprine
- Methotrexate
IVIG in some cases
Monitor CK
Describe the clinical features of Giant Cell Arteritis?
Temporal headache
Scalp tenderness
Jaw claudication
Can cause visual loss
Describe how you would investigate Giant cell arteritis?
ESR
Temporal aa biopsy
Describe the management of Giant Cell Arteritis?
High dose corticosteroids.
Start on prednisolone 40-60mg od
Continue steroids for upto 2 years gradually reducing dose providing relapse does not occur.
May need to stay on as long as 5 years
Co-prescribe: PPI and bisphosphonate
Monitor ESR and CK
Which condition is closely related to giant cell arteritis?
Polymyalgia Rheumatica (15% of patients with this develop GCA)
50-70% of patients with GCA will develop PMR
Describe the clinical features of polymyalgia rheumatica?
Presents in patients over 50yo and it is more common in caucasians.
Constitutional symptoms:
- Fatigue
- Fever
- Weight loss
Specific symptoms:
- Severe pain and stiffness in shoulders, neck and hips
- Sudden / subacute onset
- Symmetrical
- Worse in the morning: stops pt. getting out of bed
- No weakness (cf. myopathy or myositis)
Describe how you would investigate polymyalgia rheumatica?
- ESR and CRP will be significantly raised
- ALP/GGT will be raised
- CK will be normal
- ANA, RF and CCP will be negative
- May have anaemia
Describe how you would treat polymyalgia rheumatica?
Long course of corticosteroids (2 years) 10-15mg od.
Taper treatment in response to ESR
Co-prescribe: PPI and bisphosphonate
2nd line methotrexate or azothioprine
What are the non specific constitutional symptoms of Vasculitis?
- Fever
- Loss of appetite
- Weight loss
- Fatigue (tiredness)
- General aches and pains
Other symptoms are very varied depending on the type of vasculitis.
What are the specific features of Kawasaki’s, HSP, granulomatosis with polyangitis and GCA?
Kawasaki’s: In children, bright red rash
HSP: In children purpuric rash, arthritis, abdo pain, renal dysfunction
Granulomatosis with polyangitis (wegner’s): Epistaxis, haemoptysis, renal dysfunction and purpura
Giant cell arteritis: Headache, scalp tenderness, jaw claudication
How is Antiphospholipid syndrome investigated?
- ESR (norm)
- ANA (usually -ve)
- APTT (increased)
- Coombs test (positive in some)
- Anticardiolipin antibodies (diagnostic, needs to be positibe on 2 titres 12 weeks apart)
- Lupus anticoagulant antibodies (present in 20%, not a test for lupus just indicator of risk of thrombosis)
What is the difference between primary and seconary Sjorgrens syndrome?
What phenotype is sjorgrens associated with?
Primary Sjorgrens: symptoms in the absence of autoimmune disease
Secondary Sjorgrens: associated with an autoimmune disease
HLAB8/DR3
Name the different types of:
- Large vessel vasculitis
- Medium vessel vasculitis
- Small vessel vasculitis
Large: GCA, takayasu
Medium: Kawasaki, polyarteris nodosa, microscopic polyangitis
Small: HSP, Churg straus, wegners
Describe the basic prinicples of managing Vasculitis?
- Long term corticosteroids, with a gradual dose reduction
- If ANCA+ve then can use cyclophosphamide
- IVIG can be used
- Medical management of complications
How would you investigate a potential vasculitis?
BP, urine dip, FBC, LFT, CRP
c ANCA p ANCA
Tissue biopsy essential to confirm diagnosis before immunosuppression
